SOUTH SAN FRANCISCO, Calif.--(BUSINESS WIRE)--Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), announced today that new data for its approved and investigational medicines for the treatment of neurological conditions will be presented at the 71st American Academy of Neurology (AAN) Annual Meeting from May 4-10 in Philadelphia, PA. Presentations include data from a pivotal study for risdiplam in spinal muscular atrophy (SMA), which has the potential to become the first oral treatment for this community. New research for OCREVUS® (ocrelizumab) in relapsing and primary progressive multiple sclerosis shows that its effect on reducing the risk of disability progression is associated with higher exposure and lower B-cell levels. Additional OCREVUS data demonstrate the importance of earlier treatment. New data for investigational medicines in neuromyelitis optica spectrum disorder (NMOSD), Huntington’s disease (HD), Alzheimer’s disease (AD) and Duchenne muscular dystrophy (DMD) will also be shared.
“The great need for therapeutic options in areas of neuroscience such as SMA, HD and NMOSD means that every development is a collective step forward,” said Sandra Horning, M.D., chief medical officer and head of Global Product Development. “We continue to invest in research and partnerships to develop new treatment options for these diseases that severely reduce quality of life. We are pleased to contribute to the greater understanding and clinical progress of neurologic diseases at this year’s AAN Annual Meeting to help make a difference in the lives of people and families impacted by these conditions.”
Spinal Muscular Atrophy (SMA)
New data will be presented for risdiplam, an investigational oral survival motor neuron 2 (SMN2) splicing modifier for SMA, which is designed to increase and sustain SMN protein levels in the central nervous system (CNS) and throughout the body. Platform presentations include one-year data from the dose-finding Part 1 of the pivotal FIREFISH study on key motor milestones, motor function and survival in infants with Type 1 SMA. Updated safety, tolerability and pharmacokinetics / pharmacodynamics (PK/PD) data, as well as an exploratory efficacy analysis from Part 1 of the pivotal SUNFISH study in people aged 2-25 years with SMA Types 2 or 3 will also be presented.
Multiple Sclerosis (MS)
New analyses in relapsing and primary progressive multiple sclerosis suggest that higher OCREVUS exposure and lower B-cell levels are important for control of disability progression. Additionally, new long-term data from the Phase III OPERA and ORATORIO open-label extension trials showed earlier treatment with OCREVUS significantly reduced the risk of permanent disability progression. Updated safety data being presented remain consistent with findings from the controlled Phase III trials, supporting OCREVUS’ favorable benefit-risk profile.
Neuromyelitis Optica Spectrum Disorder (NMOSD)
A subgroup analysis based on AQP4-Ig serostatus from the pivotal Phase III SAkuraSky trial investigating satralizumab compared to placebo as add-on to baseline immunosuppressants and/or corticosteroids for the treatment of NMOSD will be presented. The subgroup data shows that satralizumab significantly reduced the risk of NMOSD relapse in a clinically-relevant population, especially in AQP4-Ig positive patients, with a favorable benefit-risk profile. The Phase III trial SAkuraStar, investigating satralizumab compared to placebo as a monotherapy, met its primary endpoint and will be presented at a future congress.
Satralizumab is a humanized IgG2 anti-human interleukin-6 (IL-6) receptor neutralizing monoclonal antibody that represents a novel approach to treating NMOSD by selectively inhibiting the inflammatory effects of IL-6, thought to be a key driver in the pathogenesis of the disease. There are currently no approved treatments for NMOSD, a rare, lifelong and debilitating autoimmune disease of the central nervous system that damages the optic nerve and spinal cord, causing blindness, muscle weakness and paralysis.
Huntington’s Disease (HD)
The HD platform session will include results from a translational modeling approach developed from preclinical data and includes clinical RG6042 data from the ongoing, open-label extension study in HD patients, including a safety update and mutant huntingtin (mHTT) protein reduction in the cerebrospinal fluid. These data also support the dose selection for the recently initiated Phase III GENERATION HD1 clinical trial investigating RG6042 in manifest HD.
RG6042 (formerly known as Ionis HTT-Rx) is an antisense oligonucleotide (ASO) designed to reduce the production of the toxic mHTT protein, the disease-causing protein in people with HD, by targeting human huntingtin RNA.
Alzheimer’s disease (AD)
Data and safety findings from the gantenerumab SCarlet RoAD and Marguerite RoAD open-label extension studies will be presented that show consistently large amyloid reductions in AD patients with and without ARIA-E. Genentech continues to advance the development of gantenerumab in the Phase III GRADUATE trials and the anti-tau molecule RO7105705 (MTAU9937A, RG6100) into its second Phase II clinical trial (LAURIET), which is currently enrolling patients with moderate AD.
The study design, methodology and baseline characteristics from the crenezumab Phase III CREAD study will be presented in a poster at AAN. Data from the crenezumab interim analysis of the now discontinued CREAD program were presented at the 14th International Conference on Alzheimer’s & Parkinson’s Diseases in March 2019. Additional analyses, including biomarker data, will be presented at future medical conferences. Crenezumab continues to be studied in a landmark Alzheimer’s Prevention Initiative trial of cognitively healthy individuals in Colombia with an autosomal dominant mutation who are at risk to develop familial AD (fAD).
Duchenne Muscular Dystrophy (DMD)
Results will be shared from a Phase Ib/II study of the anti-myostatin adnectin RG6206 in ambulatory boys with DMD showing no drug-related safety findings leading to withdrawal from the study through 72 weeks of treatment. RG6042 successfully lowered myostatin levels in the blood of boys with DMD and MRI and DXA imaging suggested that RG6206 had a positive effect on muscle in boys with DMD.
Stroke
Genentech recently initiated the Phase III TIMELESS trial to evaluate TNKase® (tenecteplase) in people with acute ischemic stroke (AIS) when treated from four and a half up to 24 hours after the onset of symptoms and using advanced imaging technology to identify eligible patients. There are currently no FDA approved medicines for people with AIS beyond three hours after the onset of symptoms.
Genentech’s 23-year history in AIS was established with Activase® (alteplase), the current standard-of-care in the United States, and the first and only clot-dissolving tissue plasminogen activator (tPA) approved for use in AIS for up to three hours after the onset of symptoms.
The full range of data from Genentech’s late-stage clinical development program in neuroscience being presented at AAN include:
| Medicine | Abstract Title |
Presentation Number |
||
| Risdiplam for Spinal Muscular Atrophy | FIREFISH Part 1: 1-year Results on Motor Function in Babies with Type 1 SMA Receiving Risdiplam (RG7916) |
S25.003 (platform), |
||
| Update from SUNFISH Part 1: Safety, Tolerability and PK/PD from the Dose-finding Study, Including Exploratory Efficacy Data in Patients with Type 2 or 3 Spinal Muscular Atrophy (SMA) Treated with Risdiplam (RG7916) |
S25.007 (platform), |
|||
| FIREFISH Part 1: Survival, Ventilation and Swallowing Ability in Infants with Type 1 SMA Receiving Risdiplam (RG7916) |
S25.008 (platform), |
|||
| OCREVUS (ocrelizumab) for Multiple Sclerosis | Reduction in 48-Week Confirmed Disability Progression After 5.5 Years of Ocrelizumab Treatment in Patients with Primary Progressive Multiple Sclerosis |
P3.2-031 (poster), |
||
| Long-Term Reduction in 48-Week Confirmed Disability Progression After 5 Years of Ocrelizumab Treatment in Patients with Relapsing Multiple Sclerosis |
P3.2-054 (poster), |
|||
| Evaluation of Shorter Infusion Times with Ocrelizumab in Patients with Relapsing-Remitting Multiple Sclerosis |
P3.2-034 (poster), |
|||
| Ocrelizumab Treatment Effect on Upper Limb Function in PPMS Patients with Disability: Subgroup Results of the ORATORIO Study to Inform the ORATORIO-HAND Study Design |
P3.2-091 (poster), |
|||
| Reduced Rate of Brain Atrophy in Patients with PPMS Receiving Ocrelizumab Earlier and Continuously Versus Those Initiating Ocrelizumab Later: Results of ORATORIO 5-Year Follow-Up |
P3.2-042 (poster), |
|||
| FLOODLIGHT: Smartphone-Based Self-Monitoring Is Accepted by Patients and Provides Meaningful, Continuous Digital Outcomes Augmenting Conventional In-Clinic Multiple Sclerosis Measures |
P3.2-024 (poster), |
|||
| Pharmacokinetics, Pharmacodynamics and Exposure-Response Analyses of Ocrelizumab in Patients with Multiple Sclerosis |
N4.001 (platform), |
|||
| VERISMO: A Post-Marketing Safety Study to Determine the Incidence of All Malignancies and Breast Cancer in Patients with Multiple Sclerosis Treated with Ocrelizumab |
P4.2-043 (poster), |
|||
| Safety of Ocrelizumab in Multiple Sclerosis: Updated Analysis in Patients with Relapsing and Primary Progressive Multiple Sclerosis |
P4.2-025 (poster), |
|||
| One-Year Interim Analysis Results of the Phase IIIb CHORDS Study Evaluating Ocrelizumab Effectiveness and Safety in Patients with Relapsing-Remitting Multiple Sclerosis Who Had Suboptimal Response with Prior Disease-Modifying Treatments |
S56.007 (platform), |
|||
| Ocrelizumab Treatment Reduced Levels of Neurofilament Light Chain and Numbers of B cells in the Cerebrospinal Fluid of Patients with Relapsing Multiple Sclerosis in the OBOE Study |
S56.008 (platform), |
|||
| Satralizumab for Neuromyelitis Optica Spectrum Disorder | Efficacy of Satralizumab (SA237) in Subgroups of Patients in SAkuraSky: A Phase III Double-Blind, Placebo-Controlled, Add-On Study in Patients with Neuromyelitis Optica Spectrum Disorder (NMOSD) |
S43.008 (platform), |
||
| RG6042 for Huntington’s Disease | Preliminary Reliability and Validity of a Novel Digital Biomarker Smartphone Application to Assess Cognitive and Motor Symptoms in Huntington’s Disease |
P1.8-042 (poster), |
||
| Defining Clinically Meaningful Change on the Composite Unified Huntington’s Disease Rating Scale (cUHDRS) |
P1.8-043 (poster), |
|||
| Translational Pharmacokinetic/Pharmacodynamic (PK/PD) Modelling Strategy to Support RG6042 Dose Selection in Huntington’s Disease |
S16.005 (platform), |
|||
| Gantenerumab for Alzheimer’s Disease | Consistently Large Amyloid Reductions in Patients with and Without ARIA-E in the Gantenerumab SCarlet RoAD and Marguerite RoAD Open-Label Extension Studies |
S9.007 (platform), |
||
| Crenezumab for Alzheimer’s Disease | Baseline Characteristics from a Phase III Trial of Crenezumab in Early (Prodromal-to Mild) Alzheimer’s Disease (CREAD) |
P4.1-002 (poster) |
||
| RG6206 for Duchenne Muscular Dystrophy | A Phase 1b/2 Study of the Anti-Myostatin Adnectin RG6206 (BMS-986089) in Ambulatory Boys with Duchenne Muscular Dystrophy: A 72-Week Treatment Update |
P1.6-062 (poster), |
||
Full session details and data presentation listings for the 2019 AAN Annual Meeting can be found at the meeting website: https://www.aan.com/conferences-community/annual-meeting/.
Follow Genentech on Twitter via @Genentech and keep up to date with AAN 2019 Annual Meeting news and updates by using the hashtag #AANAM.
About OCREVUS® (ocrelizumab)
OCREVUS is a humanized monoclonal antibody designed to target CD20-positive B cells, a specific type of immune cell thought to be a key contributor to myelin (nerve cell insulation and support) and axonal (nerve cell) damage. This nerve cell damage can lead to disability in people with multiple sclerosis (MS). Based on preclinical studies, OCREVUS binds to CD20 cell surface proteins expressed on certain B cells, but not on stem cells or plasma cells, and therefore important functions of the immune system may be preserved.
OCREVUS is administered by intravenous infusion every six months. The initial dose is given as two 300 mg infusions given two weeks apart. Subsequent doses are given as single 600 mg infusions.
Important Safety Information
What is OCREVUS?
OCREVUS is a prescription medicine used to treat adults with relapsing or primary progressive forms of multiple sclerosis.
It is not known if OCREVUS is safe or effective in children.
Who should not receive OCREVUS?
Do not receive OCREVUS if you have an active hepatitis B virus (HBV) infection.
Do not receive OCREVUS if you have had a life threatening allergic reaction to OCREVUS. Tell your healthcare provider if you have had an allergic reaction to OCREVUS or any of its ingredients in the past.
What is the most important information I should know about OCREVUS?
OCREVUS can cause serious side effects, including:
-
Infusion reactions: OCREVUS can cause infusion reactions that
can be serious and require you to be hospitalized. You will be
monitored during your infusion and for at least 1 hour after each
infusion of OCREVUS for signs and symptoms of an infusion reaction.
Tell your healthcare provider or nurse if you get any of these
symptoms:
- itchy skin
- rash
- hives
- tiredness
- coughing or wheezing
- trouble breathing
- throat irritation or pain
- feeling faint
- fever
- redness on your face (flushing)
- nausea
- headache
- swelling of the throat
- dizziness
- shortness of breath
- fatigue
- fast heart beat
These infusion reactions can happen for up to 24 hours after your infusion. It is important that you call your healthcare provider right away if you get any of the signs or symptoms listed above after each infusion.
If you get infusion reactions, your healthcare provider may need to stop or slow down the rate of your infusion.
-
Infection:
- OCREVUS increases your risk of getting upper respiratory tract infections, lower respiratory tract infections, skin infections, and herpes infections. Tell your healthcare provider if you have an infection or have any of the following signs of infection including fever, chills, a cough that does not go away, or signs of herpes (such as cold sores, shingles, or genital sores). These signs can happen during treatment or after you have received your last dose of OCREVUS. If you have an active infection, your healthcare provider should delay your treatment with OCREVUS until your infection is gone.
- Progressive Multifocal Leukoencephalopathy (PML): Although no cases have been seen with OCREVUS treatment in clinical trials, PML may happen with OCREVUS. PML is a rare brain infection that usually leads to death or severe disability. Tell your healthcare provider right away if you have any new or worsening neurologic signs or symptoms. These may include problems with thinking, balance, eyesight, weakness on 1 side of your body, strength, or using your arms or legs.
- Hepatitis B virus (HBV) reactivation: Before starting treatment with OCREVUS, your healthcare provider will do blood tests to check for hepatitis B viral infection. If you have ever had hepatitis B virus infection, the hepatitis B virus may become active again during or after treatment with OCREVUS. Hepatitis B virus becoming active again (called reactivation) may cause serious liver problems including liver failure or death. Your healthcare provider will monitor you if you are at risk for hepatitis B virus reactivation during treatment and after you stop receiving OCREVUS.
- Weakened immune system: OCREVUS taken before or after other medicines that weaken the immune system could increase your risk of getting infections.
Before receiving OCREVUS, tell your healthcare provider about all of your medical conditions, including if you:
- have ever taken, take, or plan to take medicines that affect your immune system, or other treatments for MS.
- have ever had hepatitis B or are a carrier of the hepatitis B virus.
-
have had a recent vaccination or are scheduled to receive any
vaccinations.
- You should receive any required ‘live’ or ‘live-attenuated’ vaccines at least 4 weeks before you start treatment with OCREVUS. You should not receive ‘live’ or ‘live attenuated’ vaccines while you are being treated with OCREVUS and until your healthcare provider tells you that your immune system is no longer weakened.
- When possible, you should receive any ‘non-live’ vaccines at least 2 weeks before you start treatment with OCREVUS. If you would like to receive any non-live (inactivated) vaccines, including the seasonal flu vaccine, while you are being treated with OCREVUS, talk to your healthcare provider.
- If you are pregnant or planning to become pregnant talk to your doctor about vaccinations for your baby, as some precautions may be needed.
- are pregnant, think that you might be pregnant, or plan to become pregnant. It is not known if OCREVUS will harm your unborn baby. You should use birth control (contraception) during treatment with OCREVUS and for 6 months after your last infusion of OCREVUS.
- are breastfeeding or plan to breastfeed. It is not known if OCREVUS passes into your breast milk. Talk to your healthcare provider about the best way to feed your baby if you take OCREVUS.
Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.
What are the possible side effects of OCREVUS?
OCREVUS may cause serious side effects, including:
- Risk of cancers (malignancies) including breast cancer. Follow your healthcare provider’s instructions about standard screening guidelines for breast cancer.
Most common side effects include infusion reactions and infections.
These are not all the possible side effects of OCREVUS. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
For additional safety information, please see the OCREVUS full Prescribing Information and Medication Guide.
For more information, go to https://www.OCREVUS.com or call 1-844-627-3887.
About TNKase®
Indication
TNKase® (tenecteplase) is indicated for use in the reduction of mortality associated with acute myocardial infarction (AMI). Treatment should be initiated as soon as possible after the onset of AMI symptoms.
Important Safety Information
Contraindications
TNKase therapy in patients with AMI is contraindicated in the following situations because of an increased risk of bleeding: active internal bleeding; history of cerebrovascular accident; intracranial or intraspinal surgery, or trauma within 2 months; intracranial neoplasm, arteriovenous malformation, or aneurysm; known bleeding diathesis; and severe uncontrolled hypertension.
Warnings
Bleeding
The most common complication encountered during TNKase therapy is bleeding. Should serious bleeding (not controlled by local pressure) occur, any concomitant heparin or antiplatelet agents should be discontinued immediately.
In clinical studies of TNKase, patients were treated with both aspirin and heparin. Heparin may contribute to the bleeding risks associated with TNKase. The safety of the use of TNKase with other antiplatelet agents has not been adequately studied. Intramuscular injections and nonessential handling of the patient should be avoided for the first few hours following treatment with TNKase.
The risk of bleeding may be increased in the following conditions and should be weighed against the anticipated benefits: recent major surgery, cerebrovascular disease, recent gastrointestinal or genitourinary bleeding, recent trauma, hypertension, high likelihood of left heart thrombus, acute pericarditis, subacute bacterial endocarditis, hemostatic defects, severe hepatic dysfunction, pregnancy, diabetic hemorrhagic retinopathy or other hemorrhagic ophthalmic conditions, septic thrombophlebitis or occluded AV cannula at seriously infected site, advanced age, patients currently receiving oral anticoagulants, recent administration of GP IIb/IIIa inhibitors, and any other condition in which bleeding constitutes a significant hazard or would be particularly difficult to manage because of its location.
Cholesterol Embolization
Cholesterol embolism has been reported rarely in patients treated with all types of thrombolytic agents; the true incidence is unknown. This serious condition, which can be lethal, is also associated with invasive vascular procedures (e.g., cardiac catheterization, angiography, vascular surgery) and/or anticoagulant therapy.
Arrhythmias
Coronary thrombolysis may result in arrhythmias associated with reperfusion. It is recommended that anti-arrhythmic therapy for bradycardia and/or ventricular irritability be available when TNKase is administered.
Use with Percutaneous Coronary Intervention (PCI)
In patients with large ST-segment elevation myocardial infarction, physicians should choose either thrombolysis or PCI as the primary treatment strategy for reperfusion.
Precautions
Standard management of myocardial infarction should be implemented concomitantly with TNKase treatment.
Pregnancy (Category C)
There are no adequate and well-controlled studies in pregnant women. TNKase should be given to pregnant women only if the potential benefits justify the potential risk to the fetus.
Nursing Mothers
It is not known if TNKase is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when TNKase is administered to a nursing woman.
Geriatric Use
In elderly patients, the benefits of TNKase on mortality should be carefully weighed against the risk of increased adverse events, including bleeding.
Adverse Reactions
The most frequent adverse reaction associated with TNKase is bleeding.
Should serious bleeding occur, concomitant heparin and antiplatelet therapy should be discontinued. Death or permanent disability can occur in patients who experience stroke or serious bleeding episodes.
For TNKase-treated patients in ASSENT-2, the incidence of intracranial hemorrhage was 0.9% and incidence of any stroke was 1.8%. The incidence of all strokes, including intracranial bleeding, increases with advancing age.
Allergic Reactions
Allergic-type reactions (e.g., anaphylaxis, angioedema, laryngeal edema, rash, and urticaria) have rarely (<1%) been reported in patients treated with TNKase. Anaphylaxis was reported in <0.1% of patients treated with TNKase; however, causality was not established.
The following adverse reactions have been reported among patients receiving TNKase in clinical trials: cardiogenic shock, arrhythmias, atrioventricular block, pulmonary edema, heart failure, cardiac arrest, recurrent myocardial ischemia, myocardial reinfarction, myocardial rupture, cardiac tamponade, pericarditis, pericardial effusion, mitral regurgitation, thrombosis, embolism, and electromechanical dissociation. These events can be life-threatening and may lead to death. Nausea and/or vomiting, hypotension, and fever have also been reported.
Please see full Prescribing Information for additional Important Safety Information.
About Activase®
Indication
Activase (alteplase) is indicated for treating patients with acute ischemic stroke (sudden stroke), which is caused by a blood clot in the brain’s blood vessels. Patients can receive Activase only if they begin treatment within 3 hours after their stroke symptoms start and only after bleeding in the brain has been ruled out.
Important Safety Information
Who should not take Activase?
Activase should not be used in patients who have: current bleeding in the brain; bleeding in the area between the brain and the thin tissues that cover the brain; active internal bleeding; recent (within 3 months) brain or spinal surgery or trauma; brain tumor, an abnormal connection between veins and arteries in the brain, or an abnormal bulge in the wall of an artery that supplies blood to the brain; problems with blood clotting; or current severe uncontrolled high blood pressure.
What are the possible serious side effects of Activase?
Bleeding: The most common side effect with Activase is bleeding. Some patients may or may not benefit from Activase because of an increased risk of bleeding, including those with the following conditions: recent major surgery; disease of blood vessels in the brain; recent bleeding in the brain; recent internal bleeding; recent trauma; uncontrolled high blood pressure; inflammation of the sac around the heart; infection of the inner lining of the heart and the heart valves; increased bleeding risk associated with liver or kidney problems; liver problems; pregnancy; bleeding in the eyes; swelling and infection associated with blood clots; elderly patients; patients on blood thinning drugs.
Allergic reaction (hypersensitivity): Allergic reactions including hives and severe or life-threatening allergic reactions can occur very quickly. Rare reports of death from severe allergic reactions have been reported. Swelling of the mouth and throat (angioedema) has been observed in patients treated for sudden stroke (acute ischemic stroke) and sudden heart attack (acute myocardial infarction). This occurred during and up to 2 hours after infusion of Activase. In many cases, patients were also taking angiotensin-converting enzyme inhibitors (a type of medication that can make blood vessels expand).
Migrated blood clot (thromboembolism): Drugs used to dissolve blood clots may be administered to patients with a high likelihood of a blood clot in the left chamber of the heart, such as patients with narrowing of a heart valve.
Cholesterol Embolization: A plug of cholesterol that blocks an artery (cholesterol embolism) has been reported rarely in patients treated with all types of clot dissolving agents. This is a serious condition, which can be lethal, and is also associated with invasive medical procedures involving the arteries and veins.
What is the most common side effect with Activase?
The most common side effect with Activase is bleeding.
Patients and their caregivers are encouraged to report side effects to Genentech and the FDA. They may contact Genentech by calling 1-888- 835- 2555. They may contact the FDA by visiting https://www.fda.gov/medwatch or calling 1-800-FDA-1088.
Please see accompanying full Prescribing Information for Activase for additional important safety information.
About Genentech in neuroscience
Neuroscience is a major focus of research and development at Genentech and Roche. The company’s goal is to develop treatment options based on the biology of the nervous system to help improve the lives of people with chronic and potentially devastating diseases. Genentech and Roche have more than a dozen investigational medicines in clinical development for diseases that include multiple sclerosis, spinal muscular atrophy, neuromyelitis optica spectrum disorder, Alzheimer’s disease, Huntington’s disease, Parkinson’s disease, Duchenne muscular dystrophy and autism.
About Genentech
Founded more than 40 years ago, Genentech is a leading biotechnology company that discovers, develops, manufactures and commercializes medicines to treat patients with serious and life-threatening medical conditions. The company, a member of the Roche Group, has headquarters in South San Francisco, California. For additional information about the company, please visit http://www.gene.com.
